Clinical lore in psychiatry has long suggested interactions between thyroid function and mood, with clinicians often reporting hypothyroidism accompanied by depressed mood in affected subpopulations. Researchers from an array of disciplines have sought to elucidate the shared pathophysiology, symptomalogy, and etiology underlying these thyroid-mood comorbidities. This review assembles recent findings in an effort to better understand the biological basis of thyroid-depression interactions. The convergence of genetic, biochemical, animal behavior, neuroimaging, and drug-related approaches holds notable promise in this developing field. Further work has implications for pharmacological augmentation in the treatment of mood and thyroid disorders.